Structural definition of a conserved neutralization epitope on HIV-1 gp120.
Zhou, T., Xu, L., Dey, B., Hessell, A.J., Van Ryk, D., Xiang, S.H., Yang, X., Zhang, M.Y., Zwick, M.B., Arthos, J., Burton, D.R., Dimitrov, D.S., Sodroski, J., Wyatt, R., Nabel, G.J., Kwong, P.D.(2007) Nature 445: 732-737
- PubMed: 17301785
- DOI: https://doi.org/10.1038/nature05580
- Primary Citation of Related Structures:
2NXY, 2NXZ, 2NY0, 2NY1, 2NY2, 2NY3, 2NY4, 2NY5, 2NY6, 2NY7 - PubMed Abstract:
The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.
Organizational Affiliation:
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.